Apelin and APJ, a novel critical factor and therapeutic target for atherosclerosis

Lv, Deguan; Li, Hening; Chen, Linxi

doi:10.1093/abbs/gmt040

Cited by 56 publications

(43 citation statements)

References 42 publications

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“…Apelin/APLNR signaling promotes angiogenesis and improves cardiac functional recovery post-myocardial infarction (19). In addition, Lv et al observed that Apelin/APLNR signaling regulates the proliferation of vascular smooth muscle cells (20), and Kasai et al found that inhibition of Apelin/APLNR signaling inhibits the proliferation of ECs (21). In the present study, the expression levels of Apelin and APLNR were found to be increased in EPCs cultured under hypoxia.…”

Section: Discussionsupporting

confidence: 59%

Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling

Zhang¹,

Liu²,

Fang³

et al. 2015

Molecular Medicine Reports

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Abstract. Endothelial progenitor cells (EPCs) can form new vessels through differentiation into endothelial cells (ECs), thus being important in the prevention of hypoxia/ischemia. Apelin can activate different signaling pathways through its receptor, APLNR, which regulate diverse biological functions, including cardiovascular function. However, the molecular mechanism by which Apelin mediates hypoxia-induced EPCs proliferation remain to be fully elucidated. The present study aimed to determine the role of Apelin/APLNR signaling in hypoxia-induced proliferation of EPCs. MTT assay was used to determine cell proliferation. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis were conducted to examine mRNA and protein expression. It was revealed that hypoxia promoted the proliferation of the EPCs. Further investigation demonstrated that hypoxia promoted the expression levels of hypoxia-inducible factor (HIF)-1α, Apelin and APLNR in the EPCs. In addition, upregulation of Apelin or APLNR promoted the hypoxia-induced proliferation of the EPCs, while knockdown of Apelin or APLNR by small interfering RNA suppressed the hypoxia-induced proliferation of the EPCs, suggesting that the Apelin/APLNR axis is involved in hypoxia-induced proliferation of EPCs. Furthermore, pretreatment of the EPCs with SB-239063 or PD98059, two inhibitors of mitogen-activated protein kinase (MAPK), eliminated the Apelin upregulation-induced EPC proliferation, suggesting that MAPK signaling is a downstream effecter of Apelin/APLNR in EPCs. Therefore, the findings of the present study indicated that the production of HIF-1α, induced by hypoxia, activated the Apelin/APLNR and the downstream MAPK signaling pathways, leading to upregulated proliferation of the EPCs. These findings suggested that Apelin/APLNR signaling may be used as a potential therapeutic target for hypoxic/ischemic injury.

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Section: Discussionsupporting

confidence: 59%

Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling

Zhang¹,

Liu²,

Fang³

et al. 2015

Molecular Medicine Reports

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“…On the other hand, novel papers focused on contribution of apelin to atherosclerosis triggered by dyslipidemia. [39][40][41] Despite the lack of cardiovascular and atherosclerotic investigations in our study, the strong relationship found between apelin and lipids suggested that apelin might be a target for preventing hyperlipidemia and subsequent atherosclerotic processes in patients with ESRD.…”

Section: Discussionmentioning

confidence: 99%

Apelin and nutritional status in children on dialysis

et al. 2014

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Background: We aimed to evaluate whether serum apelin could reflect the nutritional status of children on dialysis. Methods: Twelve patients on peritoneal dialysis (PD) and 20 patients on hemodialysis (HD) were enrolled. Patients received individualized diet for six months. Anthropometric and laboratory indices were measured at onset and the end of the study. Results: The anthropometric indices were all significantly lower in patients than in controls whereas similar in PD and HD patients. The protein catabolic rate (nPCR), height, mid-arm circumference (MAC), triceps skinfold thickness (TSF), arm muscle area (AMA) and arm fat area (AFA) z scores were significantly increased in dialysis patients after nutritional intervention. Weight z scores statistically increased in HD group whereas did not statistically change in PD group. Serum albumin levels were significantly improved in PD and HD patients. Apelin levels were similar in PD, HD and control groups. Post nutritional apelin values did not differ in each dialysis groups. On multivariate analysis, apelin was independently associated with age, weight, ESR and TG. Conclusions: Apelin seems to be not a useful indicator for monitoring the nutritional status in children on dialysis. However, the close link of apelin with inflammatory and lipid parameters suggested that apelin might be a novel target for slowing the atherogenic process in pediatric dialysis patients.

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“…It was discovered in 1993 via homology cloning [164,165] . Apelin-13/APJ system has been identified as a potential therapeutic target for hypertension [166] and atherosclerosis [167] . Our laboratory has demonstrated that apelin-13 induced proliferation of vascular smooth muscle cells [66,168] and rat bone marrow-derived mesenchymal stem cells [169] through the Jagged-1/Notch3, cyclin D1 and AKT/ GSK3β/cyclin D1 pathways.…”

Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

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Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.

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Apelin and APJ, a novel critical factor and therapeutic target for atherosclerosis

Cited by 56 publications

References 42 publications

Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling

Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling

Apelin and nutritional status in children on dialysis

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

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